Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, 91120, Israel.
The Department of Neurology and Laboratory of Neuroimmunology, The Agnes-Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, Ein-Kerem P.O.B. 12000, Jerusalem, 91120, Israel.
Mol Neurodegener. 2024 Jul 12;19(1):53. doi: 10.1186/s13024-024-00742-8.
Multiple sclerosis (MS) therapeutic goals have traditionally been dichotomized into two distinct avenues: immune-modulatory-centric interventions and pro-regenerative strategies. Oligodendrocyte progenitor cells (OPCs) were regarded for many years solely in concern to their potential to generate oligodendrocytes and myelin in the central nervous system (CNS). However, accumulating data elucidate the multifaceted roles of OPCs, including their immunomodulatory functions, positioning them as cardinal constituents of the CNS's immune landscape.
In this review, we will discuss how the two therapeutic approaches converge. We present a model by which (1) an inflammation is required for the appropriate pro-myelinating immune function of OPCs in the chronically inflamed CNS, and (2) the immune function of OPCs is crucial for their ability to differentiate and promote remyelination. This model highlights the reciprocal interactions between OPCs' pro-myelinating and immune-modulating functions. Additionally, we review the specific effects of anti- and pro-inflammatory interventions on OPCs, suggesting that immunosuppression adversely affects OPCs' differentiation and immune functions.
We suggest a multi-systemic therapeutic approach, which necessitates not a unidimensional focus but a harmonious balance between OPCs' pro-myelinating and immune-modulatory functions.
多发性硬化症 (MS) 的治疗目标传统上分为两条截然不同的途径:免疫调节为中心的干预和促再生策略。少突胶质前体细胞 (OPC) 多年来仅因其在中枢神经系统 (CNS) 中产生少突胶质细胞和髓鞘的潜力而受到关注。然而,越来越多的证据表明 OPC 具有多方面的作用,包括其免疫调节功能,将其定位为 CNS 免疫景观的主要组成部分。
在这篇综述中,我们将讨论这两种治疗方法如何融合。我们提出了一个模型,即(1)在慢性炎症的 CNS 中,炎症对于 OPC 适当的促髓鞘形成免疫功能是必需的,以及(2)OPC 的免疫功能对于其分化和促进髓鞘再生的能力至关重要。该模型强调了 OPC 促髓鞘形成和免疫调节功能之间的相互作用。此外,我们回顾了抗炎和促炎干预对 OPC 的具体影响,表明免疫抑制会对 OPC 的分化和免疫功能产生不利影响。
我们建议采取多系统治疗方法,这需要的不是单一维度的关注,而是 OPC 促髓鞘形成和免疫调节功能之间的和谐平衡。